δ阿片类药物SNC 80提高荷瘤小鼠的存活率。

Increased survival of tumor-bearing mice by the delta opioid SNC 80.

作者信息

Gomez-Flores Ricardo, Caballero-Hernández Diana, Tamez-Guerra Reyes, Rodríguez-Padilla Cristina, Tamez-Guerra Patricia, Rice Kenner C, Hicks Mary E, Weber Richard J

机构信息

Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, NL, México.

出版信息

Anticancer Res. 2005 Nov-Dec;25(6C):4563-7.

PMID:16334142

Abstract

Opioids represent a major source of relief from pain. However, opioid abuse may cause immunosuppression and cancer. We have recently reported results on novel non-peptidic delta- and mu-selective opioids that induced immunopotentiation of T cell and macrophage functions in vitro and ex vivo. In the present study, the effects of the delta-opioid receptor agonist and potent analgesic (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC80) on in vitro and in vivo tumor cell growth were investigated using the L5178Y-R murine model. SNC80 marginally, but significantly (p < 0.05), inhibited (up to 14%) the in vitro growth of L5178Y-R tumor cells. However, in vivo intratumor administration of SNC80 (2 and 4 mg/kg) reduced up to 60% L5178Y-R tumor-bearing Balb/c mice death, and significantly (p < 0.05) reduced tumor weights (up to 73% reduction) in these animals. This study may support the evaluation of SNC80 in preclinical and clinical studies.

摘要

阿片类药物是缓解疼痛的主要来源。然而，阿片类药物滥用可能导致免疫抑制和癌症。我们最近报道了新型非肽类δ和μ选择性阿片类药物的研究结果，这些药物在体外和体内均可诱导T细胞和巨噬细胞功能的免疫增强。在本研究中，使用L5178Y-R小鼠模型研究了δ阿片受体激动剂和强效镇痛药(+)-4-((αR)-α-((2S,5R)-4-烯丙基-2,5-二甲基-1-哌嗪基)-3-甲氧基苄基)-N,N-二乙基苯甲酰胺(SNC80)对体外和体内肿瘤细胞生长的影响。SNC80对L5178Y-R肿瘤细胞的体外生长有轻微但显著的抑制作用(p<0.05)(抑制率高达14%)。然而，在体内向肿瘤内注射SNC80(2和4mg/kg)可使携带L5178Y-R肿瘤的Balb/c小鼠死亡率降低多达60%，并显著(p<0.05)降低这些动物的肿瘤重量(降低率高达73%)。本研究可能支持在临床前和临床研究中对SNC80进行评估。